| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 14.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10037153 |
| E.1.2 | Term | Psoriasis |
| E.1.2 | System Organ Class | 10040785 - Skin and subcutaneous tissue disorders |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
-To compare the efficacy responses of CP-690,550 (5 mg BID and 10 mg BID) versus
placebo following 24 weeks of CP-690,550 treatment and subsequent withdrawal of
active treatment at various timepoints during the 16-week double-blind active or
placebo treatment period in subjects with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy.
-To evaluate the regain of efficacy responses of CP-690,550 (5 mg BID and 10 mg
BID) following 4-16 weeks of CP-690,550 treatment withdrawal and subsequent
re-treatment in subjects with moderate to severe chronic plaque psoriasis who are
candidates for systemic therapy or phototherapy.
-To evaluate the safety and tolerability of CP-690,550 (5 mg BID and 10 mg BID) in
subjects with moderate to severe chronic plaque psoriasis who are candidates for
systemic therapy or phototherapy. |
|
| E.2.2 | Secondary objectives of the trial |
- To evaluate the efficacy of CP-690,550 (5 mg BID and 10 mg BID) for the reduction in severity of plaque psoriasis at various timepoints during 56 weeks of treatment in subjects with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy.
- To evaluate the effects of CP-690,550 (5 mg BID and 10 mg BID) on patient reported outcome (PRO) measures at various timepoints during 56 weeks of treatment in subjects with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
| Subjects must meet all of the following inclusion criteria to be eligible for enrolment into the study: 1. Evidence of a personally signed and dated informed consent document indicating the subject (or legal representative) has been informed of all pertinent aspects of the trial. 2. Willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures. 3. Be at least 18 years of age at time of informed consent. 4. Have had a diagnosis of plaque-type psoriasis (psoriasis vulgaris) for at least 12 months prior to first dose of study drug. 5. Have a PASI score of 12 or greater AND a PGA score of 3 (moderate) or 4 (severe) at Baseline. 6. Have plaque-type psoriasis covering at least 10% of total body surface area at Baseline. 7. Considered by investigator to be a candidate for systemic therapy or phototherapy of psoriasis (either naïve or history of previous treatment). 8. Sexually active women of childbearing potential are required to use adequate contraceptive methods during study participation. 9. No evidence of active or latent or inadequately treated infection with Mycobacterium tuberculosis (TB) as defined by all of the following: - A negative QuantiFERON®-TB Gold (QFT-G) In-Tube test or, if unavailable or indeterminate upon retest a negative Mantoux Purified Protein Derivative (PPD) tuberculin skin test (according to local standard 48 to 72 hours after injection) at or within the 3 months prior to a given Screening visit. Chest radiographs, taken at or within the 3 months prior to a given Screening visit, without changes suggestive of active TB infection as determined by a qualified radiologist; No history of either untreated or inadequately treated latent or active TB infection; If a subject has previously received an adequate course of therapy for either latent (9 months of isoniazid in a locale where rates of primary multi-drug TB resistance are <5% or an acceptable alternative regimen) or active (acceptable multi-drug regimen) TB infection, neither a QFT-G test nor a PPD test need be obtained, but chest radiographs must still be obtained if not performed within 3 months prior to a given Screening visit. Documentation of adequate treatment for TB will be obtained prior to first dose of study drug. A subject who is currently being treated for active TB infection is to be excluded. A subject who is currently being treated for latent TB infection can only be enrolled with confirmation of current incidence rates of multi-drug resistant TB infection in the locale, documentation of an adequate treatment regimen, and with prior approval by the Sponsor. 10. Must agree to avoid prolonged exposure to the sun and avoid use of tanning booths or other ultraviolet light sources during the study. 11. Non-prohibited concomitant medications must be on a stable regimen, which is defined as not starting a new drug or changing dosage within 7 days or 5 half-lives (whichever is longer) prior to first dose of study drug. Subject must be willing to stay on a stable regimen. 12. If received any of the following treatment regimens, for any reason, are eligible providing the following minimum washout criteria are observed: Must be discontinued for at least 12 weeks prior to first dose of study drug: a. Any investigational or experimental therapy or procedure for psoriasis, psoriatic arthritis or rheumatoid arthritis; Exception: Investigational biologics should be discussed with the Pfizer Medical Monitor (or designee) to confirm period of discontinuation required b. Ustekinumab. Must be discontinued for at least 8 weeks prior to first dose of study drug: a. Adalimumab; b. Infliximab; c. Alefacept. Must be discontinued for at least 4 weeks prior to first dose of study drug: a. Etanercept; b. Systemic treatments other than biologics that could affect psoriasis, eg, oral or injectable (eg, intraarticular, intramuscular, or intravenous) corticosteroids, retinoids, methotrexate, cyclosporine, fumaric acid derivatives, sulfasalazine, hydroxycarbamide (hydroxyurea), azathioprine, intramuscular gold;c. Psoralens + UVA phototherapy (PUVA). Must be discontinued for at least 2 weeks prior to first dose of study drug: a. Topical treatments that could affect psoriasis, eg, corticosteroids, tars, keratolytics, anthralin, vitamin D analogs, and retinoids; Exceptions – the following topical treatments are allowed: non-medicated emollients for use over the whole body; low or least potent (Class 6 or 7) topical corticosteroids for the palms, soles, face, and intertriginous areas only; tar and salicylic acid preparations for the scalp only, and shampoos free of corticosteroids for the scalp only; b. UVB (narrowband or broadband) phototherapy. Note: per exclusion criterion, prior treatment with efalizumab is exclusionary. |
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| E.4 | Principal exclusion criteria |
1. Currently have non-plaque forms of psoriasis, eg, erythrodermic, guttate, or pustular; nail psoriasis is allowed. 2. Have skin conditions that would interfere with evaluation of psoriasis. 3. Have drug-induced new onset or an exacerbation of psoriasis from beta blockers, calcium channel blockers, antimalarial drug, or lithium. 4. Have planned initiation of or changes to concomitant medication that could affect psoriasis (eg, beta blockers, calcium channel blockers, antimalarial drugs, or lithium) within 2 weeks prior to randomization or during the study. 5. Cannot discontinue systemic, topical or photo (UVB or PUVA) therapies for treatment of psoriasis. 6. Are taking or require oral or injectable corticosteroids for any condition. 7. Laboratory values during Screening visit(s): a. Hemoglobin <11.0 g/dL or hematocrit <30%; b. White blood cell count <3.0 x 10 to the power of 9/L; c. Absolute neutrophil count of <1.5 x 10 to the power of 9/L; d. Platelet count <100 x 10 to the power of 9/L; e. estimated creatinine clearance <40 mL/min based on the Cockcroft-Gault calculation or creatinine greater than 1.5 times the upper limit of normal (ULN); f. Aspartate or alanine aminotransferase values more than 2xULN; g. Any uncontrolled clinically significant laboratory abnormality that would affect interpretation of study data or the subject’s study participation. 8. Women who are pregnant or lactating, or planning pregnancy while enrolled. 9. Have current or recent severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, metabolic, endocrine, pulmonary, cardiovascular, or neurological disease. 10. Have a history of any lymphoproliferative disorder, lymphoma, leukemia, or signs and symptoms suggestive of current lymphatic disease. 11. Had single episode of disseminated herpes zoster or disseminated herpes simplex, or a recurrent localized, dermatomal herpes zoster. 12. Had infection requiring hospitalization, parenteral antimicrobial therapy, or otherwise judged clinically significant by the investigator within 6 months prior to first dose of study drug. 13. Had infection requiring antimicrobial therapy within 2 weeks prior to first dose of study drug. 14. Vaccinated with live or attenuated live vaccine within the 6 weeks prior to the first dose of study drug, or expects to be vaccinated with these vaccines during the study or during the 6 weeks following the last dose of study drug. 15. Any prior treatment with non B cell-specific lymphocyte depleting agents/therapies. Subjects who received rituximab or other selective B-lymphocyte depleting agents (including experimental agents) are eligible if they have not received such therapy for at least 1 year prior to first dose of study drug and have normal CD19/20+ counts by FACS analysis. 16. Have previously been treated with efalizumab. 17. Previously participated in a study of oral CP-690,550. 18. Have any condition possibly affecting oral drug absorption, eg, gastrectomy, clinically significant diabetic gastroenteropathy, or certain types of bariatric surgery such as gastric bypass. 19. Have a history of alcohol or substance abuse, unless in full remission for greater than 6 months prior to first dose of study drug. 20. A Screening or Baseline ECG that demonstrates clinically relevant abnormalities which may affect subject safety or interpretation of study results. 21. Have a known immunodeficiency disorder or a first-degree relative with hereditary immunodeficiency. 22. Have malignancies or history of malignancies with the exception of adequately treated or excised nonmetastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ. 23. Have undergone significant trauma or major surgery within 1 month prior to screening. 24. Require treatment with prohibited concomitant medication(s) or have received a prohibited concomitant medication within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study drug. 25. Known to be infected with human immunodeficiency virus, hepatitis B or hepatitis C viruses 26. Have participated in other studies using an investigational therapy or procedure within 4 weeks or 5 half-lives (whichever is longer) prior to the first dose of study drug. Any investigational therapy or procedure for psoriasis, psoriatic arthritis or rheumatoid arthritis must be discontinued for at least 12 weeks prior to first dose of study drug. Subjects cannot participate in studies of other investigational therapies or procedures at any time during their participation in the study. 27. Have any other severe medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration. 28. Subjects who are investigational site staff members or subjects who are Pfizer employees directly involved in the conduct of the trial.29. A subject who will be
uncooperative or unable to comply with study procedures. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
1. Proportion of subjects maintaining a Psoriasis Area and Severity Index 75 (PASI75) response (at least a 75% reduction in Psoriasis Area and Severity Index relative to baseline/day 1) during the 16 week double blind active or placebo treatment period (CP 690,550 treatment withdrawal; Period B). 2. Proportion of subjects maintaining a Physician’s Global Assessment (PGA) response (PGA of “clear” or “almost clear”) during the 16 week double blind active or placebo treatment period (CP 690,550 treatment withdrawal; Period B). 3. Among subjects who had a >50% reduction of the Visit A4/Week 24 PASI response during CP 690,550 treatment withdrawal, the proportion of subjects achieving a PASI75 response during CP 690,550 re treatment (Period C). 4. Among subjects who had a PGA of “mild”, “moderate”, or “severe” during CP 690,550 withdrawal, the proportion of subjects achieving a PGA response (PGA of “clear” or “almost clear”) during CP 690,550 re treatment (Period C). - Proportion of subjects with rebound (defined as worsening of psoriasis over baseline
[Day 1, Visit A0] value [PASI>125%] or new type of psoriasis [pustular, erythrodermic, as reported on adverse event forms]) during the period between Week 24 (Visit A4) and Week 32 (Visit B2). |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Week 24-40 and Week 28-56. |
|
| E.5.2 | Secondary end point(s) |
Time to PASI75 response during initial CP-690,550 treatment (Period A).
• Time to PGA response during initial CP-690,550 treatment (Period A).
• Time to loss of adequate response, defined as >50% reduction of the Visit A4/Week
24 PASI response during the 16-week double-blind active or placebo treatment period
(CP-690,550 treatment withdrawal; Period B);
• Proportion of subjects with rebound (defined as worsening of psoriasis over baseline
[Day 1, Visit A0] value [PASI>125%] or new type of psoriasis [pustular,
erythrodermic, as reported on adverse event forms]) during the period between Week
24 (Visit A4) and Week 32 (Visit B2).
• Proportion of subjects with worsening of psoriasis over baseline [Day 1, Visit A0]
value (percent change from baseline PASI>125%) or new type of psoriasis (pustular,
erythrodermic, as reported on adverse event forms) during the 16-week double-blind
active or placebo treatment period (CP-690,550 treatment withdrawal; Period B).
• Time to loss of at least 50% of the Visit A4/Week 24 PASI response and loss of PGA
response (PGA of ‘clear’ or ‘almost clear’) during the 16 week double blind active or
placebo treatment period (CP 690,550 treatment withdrawal; Period B).
• Time to regain PASI75 and PGA response (PGA of ‘clear’ or ‘almost clear’) during
CP 690,550 re treatment (Period C).
• The proportion of subjects regaining PASI75 and PGA response (PGA of ‘clear’ or
‘almost clear’) during CP 690,550 re treatment (Period C).
• Time to PASI75 response during CP-690,550 re-treatment (Period C).
Time to PGA response during CP-690,550 re-treatment (Period C).
• PASI75 response at various timepoints through Week 56.
• PGA response at various timepoints through Week 56.
• Actual and change from baseline in PASI and PASI component scores at various
timepoints through Week 56.
• Proportion of subjects achieving at least a 50% and 90% reduction in PASI relative to
baseline (PASI50 and PASI90, respectively) at various timepoints through Week 56.
• Proportion of subjects with a PASI score 125% of the baseline PASI score at various
timepoints through Week 56.
• Proportion of subjects in each PGA category at various timepoints through Week 56.
• Actual and change from baseline in the Itch Severity Item (ISI) score at various
timepoints through Week 56.
• Actual and change from baseline on the Dermatology Life Quality Index (DLQI)
score at various timepoints through Week 56.
• Other patient reported outcome (PRO) measures to be assessed at various timepoints
through Week 56.
• Short Form-36 (Version 2, Acute) (SF-36);
• Patient Global Assessment of Psoriasis (PtGA);
• EuroQol 5 Dimensions (EQ-5D).
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Baseline to Week 24, Week 24-40 and Week 28-56.
|
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
| Tolerability. Pharmacogenetic & pharmacogenomic research components explored in molecular profiling |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
| Mixed Blind: 2 study periods that are dose-blind and 1 study period that is double-blind |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 4 |
| E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 25 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Argentina |
| Australia |
| Brazil |
| Bulgaria |
| Canada |
| Denmark |
| Finland |
| Greece |
| Italy |
| Netherlands |
| Slovakia |
| United Kingdom |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| End of Trial in a Member State of the European Union is defined as the time at which it is deemed that sufficient subjects have been recruited and completed the study as stated in the regulatory application (ie, Clinical Study Application (CTA)) and ethics application in the Member State. Poor recruitment (recruiting less than the anticipated number in the CTA) by a Member State is not a reason for premature termination but is considered a normal conclusion to the study in that Member State. |
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 1 |
| E.8.9.2 | In all countries concerned by the trial days | 4 |
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